To Ablate Or Not To Ablate Final Shortened - Handout.ppt Ablate Or... · CV hospitalizations or...

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John Hummel, MDDirector of Electrophysiology Research

Professor – ClinicalDepartment of Internal Medicine

Division of Cardiovascular MedicineThe Ohio State University Wexner Medical Center

To Ablate or Not to Ablate: Current Management of Atrial

Fibrillation

AF: Growing Health ProblemAF: Growing Health Problem

• Projected that the number of persons with AF in the U.S. will exceed 10 million by the year 2050

• Atrial fibrillation is a well established risk factor for:

‒ Stroke

‒ Congestive heart failure

‒ Premature death

Renfrew / Paisley Study: Long-Term Risks Associated with AFRenfrew / Paisley Study: Long-Term Risks Associated with AF

Stewart S et al. Am J Med. 2002;113:359-64.

N = 15,856 aged 45–64 years

Year of follow-up

CV hospitalizations or deaths Mortality

Eve

nt-

fre

e s

urv

iva

l p

rob

ab

ility

*

Su

rviv

al

pro

ba

bili

ty*

Men AF

Women AF

Men no AF

Women no AF

Men AFWomen AF

Women no AF

*Age-adjusted

Men no AF

https://doi.org/10.1016/S0002-9343(02)01236-6

Manitoba Follow-Up Study: Effect of AF on Morbidity and Mortality

Manitoba Follow-Up Study: Effect of AF on Morbidity and Mortality

EndpointCohort

(n) After AF (n)Relative risk

(95% CI)

Total mortality 1603 136 1.31 (1.08–1.59)

CV mortality 662 92 1.41 (1.11–1.80)

Stroke mortality 83 15 2.48 (1.35–4.57)

Nonstroke CV mortality 579 77 1.37 (1.05–1.78)

Non-CV mortality 941 44 1.10 (0.80–1.53)

Stroke 371 32 2.07 (1.43–3.01)

Congestive heart failure 258 35 2.98 (2.09–4.26)

Myocardial infarction 590 19 1.02 (0.64–1.54)

Krahn AD et al. Am J Med. 1995;98:476-84.

N = 3983 male air crew recruits observed continuously for 44 years

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Afib and the Risk of DementiaAfib and the Risk of Dementia

Santangeli, et al, Heart Rhythm 2012https://doi.org/10.1016/j.hrthm.2012.07.026

Dementia, AF and Cerebral Blood FlowDementia, AF and Cerebral Blood Flow4251 pts from Icelandic population:

Association between AF and lower brain volume and gray matter.

2291 Patients in the AGES-Reykjavik Study underwent assessment of blood flow in cervical arteries with phase contrast MRI and brain perfusion estimated.

3 Groups: PersAF, PAF and no Hx of AF at the time of the MRISimilar with regard to cardiovascular risk factors.

Gardarsdottir et. Al, Europace 2016

QOL Changes AF SRQOL Changes AF SR

Symptomatic Patients

Asymptomatic Patients

https://doi.org/10.1016/j.jacc.2006.03.051 The AFFIRM Investigators. N Engl J Med. 2002;347:1825-1833.

AFFIRM Trial: Rate vs Rhythm ControlManagement Strategy Trial

AFFIRM Trial: Rate vs Rhythm ControlManagement Strategy Trial

• Design‒ 5-year, randomized, rate control vs. AARx ‒ Primary endpoint: overall mortality

• Patient population‒ 4060 patients with AF and risk factors for stroke‒ Minimal symptoms‒ Mean Age = 69 yo‒ Hx of hypertension: 70.8%‒ CAD: 38.2%‒ Enlarged LA: 64.7%‒ Depressed EF: 26.0%

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Medical Treatment in AFFIRM:Medical Treatment in AFFIRM:

0

5

10

15

20

25

30

0 1 2 3 4 5

Mo

rtal

ity,

%

RateRhythm

p=0.078 unadjusted

Time (years)

p=0.068 adjusted

The AFFIRM Investigators. N Engl J Med. 2002;347:1825-1833.

Do these unabated increases in mortality simply represent equally poor therapies allowing CHF, Stroke, and Declines in Cognition to progress?

100 –

80 –

60 –

40 –

20 –

0 –

Time (years)

PercentWith AF

Recurrence

Rate Control

Raitt, et al. Am H J 2006

0 1 2 3 4 5 6

Time to Recurrence of AF in Affirm

Rhythm Control

Log rank statistic = 58.62

p < 0.0001

% NSR at End of Trial: Affirm 63%, Race 39%, PIAF 56%, STAF 26%

Risk of Death in Affirm: Is Sinus Rhythm the Goal?

Risk of Death in Affirm: Is Sinus Rhythm the Goal?

*HR <1.00: Decreased risk of death, HR >1.00: Increased risk of death

AFFIRM Investigators. Circulation. 2004;109:1509-13.

AFFIRM: Selected time-dependent covariates associated with survival

Sinus rhythm <0.0001 0.53 0.39–0.72

Warfarin <0.0001 0.50 0.37–0.69

Digoxin 0.0007 1.42 1.09–1.86

Antiarrhythmic 0.0005 1.49 1.11–2.01

Covariate P Hazard ratio* 99% CI

AF Wreaks Havoc in CHFAF Wreaks Havoc in CHF• AF in HF patients increases the 3-

year risk of:

‒ mortality (hazard ratio 1.13)

‒ all-cause readmission (HR, 1.15)

‒ HF (HR, 1.22)

‒ stroke (HR, 1.57).

• New-onset AF in CHF pts convey a greater increased risk

• The adverse impact of AF on mortality in HF greatest in mild-to-moderate HF.

McManus et. Al, JAHA 2013

If NSR is Beneficial for Most People, it Should be Easy to See In the CHF Population

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AFCHFAFCHF

• 1376 pts. with LVEF ≤ 35%, symptomatic CHF, and Hx/o AF

• 682 in the rhythm-control group, 694 in the rate-control group

• Primary Outcome: Death from CV causes

• Amiodarone 82% of rhythm control medication

• ~ 70% of patients in NSR at 2 years

• No Difference In:

‒ Death from any cause

‒ Stroke

‒ Heart Failure Hospitalization

‒ Composite outcome

Roy et. Al, NEJM 2008

COMET: Effect of Amiodarone on All-cause Mortality

COMET: Effect of Amiodarone on All-cause Mortality

COMET = Carvedilol or Metoprolol European Trial

Torp-Pedersen C et al. J Card Failure. 2007;13:340-5.

N = 3029 with chronic HF randomized to carvedilol or metoprolol Median follow-up 58 months

https://doi.org/10.1016/j.cardfail.2007.02.009

Catheter Ablation as the Initial Rhythm Control Strategy


SUCCESS RATES

American Heart Association. Ablation Versus Drugs: What Is the Best First-Line Therapy for Paroxysmal Atrial Fibrillation? Pasquale Santangeli, MD, Luigi Di Biase, MD, PhD, and Andrea Natale, MD

© Copyright 2014 American Heart Association, Inc.



COMPLICATIONS



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Costs



An initial AF episode of 30 seconds does not predict clinically meaningful AF patterns, > 3.8 hours did.

American Heart Association. Thirty-Second Gold Standard Definition of Atrial Fibrillation and Its Relationship With Subsequent Arrhythmia Patterns. Jonathan S. Steinberg, MD, Heather O’Connell, MS, Shelby Li, MD, MS and Paul D. Ziegler, MS


AF and CHF Ablation TrialsAF and CHF Ablation Trials

Baher et. Al, AER-Volume 7, Issue 2, 2018

Out of 7 trials and 650 patients only one trial found no benefit

https://doi.org/10.15420/aer.2018.17.2

Afib Ablation In CHF: Castle CHFAfib Ablation In CHF: Castle CHF

Marrouche et al, NEJM 2018

• 397 pts with AF and LVEF ≤35%

• Randomized to RFA or AArx. Mean FU 38 months

• Primary endpoint: composite of all-cause mortality and hospitalization for worsening CHF.

• Results:

• Composite endpoint was significantly lower in the ablation (28.5 percent) vs. control (44.6 percent) over period of 37.8 months.

• Secondary endpoints:

– all-cause mortality in ablation 13% vs. 25%

– heart failure hospitalization significantly lower in ablation group 21% vs. 36%

https://doi.org/10.1056/NEJMoa1707855

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Relative Risk of Ablation vs. MedicationRelative Risk of Ablation vs. Medication

AF Ablation• Stroke

• Phrenic Nerve Paralysis

• Vascular Complication

• Esophageal Injury

• Valve Injury

• Chest Pain

Medication• Life threatening

arrhythmia

• CHF

• Liver toxicity

• Thyroid toxicity

• Headache

• Fatigue

Catheter ABlation vs ANtiarrhythmic Drug Therapy in Atrial Fibrillation - CABANA


• Description:

• Goal: Compare the safety and efficacy of catheter ablation with drug therapy for treatment of new-onset or untreated atrial fibrillation (AF).

• Study Design

• Pts randomized in a 1:1 fashion to catheter ablation (n = 1,108) or drug therapy (n = 1,096).

• Duration of follow-up: 5 years

• Mean patient age: 67.5 years

• Percentage female: 37%

• Inclusion criteria:

Presented by Dr. D.Packer at HRS 2018



• Study Design

• Paroxysmal, persistent, or longstanding persistent AF patients who warrant therapy

• ≥65 years of age

• <65 years of age with ≥1 cerebrovascular accident (CVA)/cardiovascular (CV) risk factor

• Eligible for ablation

• On ≥2 rhythm or rate control drugs

Other Salient Features/Characteristics:Other Salient Features/Characteristics:

• Cardiomyopathy: 9%

• Chronic heart failure: 15%

• Prior CVA/transient ischemic attack (TIA): 10%

• Type of AF: paroxysmal: 43%, persistent 47%

• Prior hospitalization for AF: 39%

• Crossover: ‒ ablation to drug: 9.2%‒ drug to ablation: 27.5%

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ITT OutcomesITT Outcomes• The primary outcome [death, disabling stroke, serious

bleeding, or cardiac arrest] at 5 years:‒ ablation = 8%‒ drug therapy = 9.2%, p = 0.3

• Death: 5% vs. 6% for ablation vs. drug therapy, p = 0.38• Serious stroke: 0.3% vs. 0.6% for ablation vs. drug

therapy, p = 0.19• Death or CV hospitalization:

51.7% vs. 58.1% for ablation vs. drug therapy, HR 0.83, 95% CI 0.74-0.93, p = 0.002

• Primary endpoint ‒ Ablation=7%‒ Drug Therapy=10.9% p=0.006

• Death: 4.4% vs. 7.5% for ablation vs. drug therapy: p = 0.005

• Death or CV hospitalization: 41.2% vs. 74.9% for ablation vs. drug therapy: p = 0.002

Outcomes Based on Treatment Received

Cabana ConclusionsCabana Conclusions• Catheter ablation did not result in reduction in

primary endpoint over drug therapy

• Ablation significantly reduced combined mortality or hospitalization by 17% over drug therapy

• There was a 47% reduction in AF with ablation compared to drug therapy

• There was a 40% reduction in mortality and a 33% reduction in the primary endpoint with ablation in on-treatment analysis.

Prolongation of the duration electrically induced episodes of atrial fibrillation (AF) after maintaining AF for 24 hours vs. 2 weeks.

Prolongation of the duration electrically induced episodes of atrial fibrillation (AF) after maintaining AF for 24 hours vs. 2 weeks.

American Heart Association. Atrial Fibrillation Begets Atrial FibrillationMaurits C.E.F. Wijffels , MD , Charles J.H.J. Kirchhof , MD, PhD , Rick Dorland , BS , and Maurits A. Allessie , MD, PhD


AF begets AFAF begets AFAF itself causes arrhythmogenic milieu that further promotes and maintains AF:

‒ Atrial electrical remodeling • Atrial ERP, spatial

heterogeneity of ERP, normal ERP rate adaptation

• Slow conduction – Modulation of Na

channels, gap junctions (connexins), altered tissue structure

‒ Structural remodeling • Macro-atrial dilation• Micro-atrial fibrosis

https://doi.org/10.1016/j.pbiomolbio.2012.07.011

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Spectrum of DiseaseAt Different Stages of AF, Different Sustaining

Mechanisms May Dominate

Spectrum of DiseaseAt Different Stages of AF, Different Sustaining

Mechanisms May Dominate

de-Groot et al, Circ Arrhythmia 2016

Endo-Epi Asynchrony

Degrees of Fibrosis (Sirius Red stained paraffin sections)

Degrees of Cell Degeneration (hematoxyline– eosin)

W. Anne´ et al. / Cardiovascular Research 67 (2005)Kottkamp et al; JCE 2016

More advanced remodeling may not reverse after resumption of NSR

https://doi.org/10.1016/j.cardiores.2005.04.016

American Heart Association. Direct Proof of Endo-Epicardial Asynchrony of the Atrial Wall During Atrial Fibrillation in Humans. Natasja de Groot, MD, et al © Copyright 2016 American Heart Association, Inc.

Does the Form of AF Management Affect LA Remodeling?

Does the Form of AF Management Affect LA Remodeling?

• With PAF:‒ risk of Persistent AF 15% at one year ‒ risk of Persistent AF 25% at 5 years

• Conflicting data as to whether AF-associated remodeling reverses after effective ablation vs. medical management

• The progression or regression of atrial remodeling over a 12-month period with medical management or catheter ablation was assessed in 83 patients

• Prospective, nonrandomized cohort analysis

Walters et al, Heart Rhythm, Vol 13, No 2, February 2016

Remodeling of LA With Different Forms of Management

Remodeling of LA With Different Forms of Management

• 83 pts recruited into 3 groups:‒ PAF undergoing medical management (group 1,n = 38)‒ PAF undergoing ablation (group 2,n = 20)‒ Control pts without Hx of AF(group 3,n = 25).

• Two blinded, baseline assessments of:‒ BP,anthropometric measurements, ‒ Digital ECG (with P wave duration and dispersion)‒ TTE assessment of myocardial strain (total and peak

positive strain taken to be indirect markers of LA structural remodeling and of atrial myocardial fibrosis)

‒ Sleep evaluation• Ablation patients evaluated for LA voltage, LA activation

times• Repeat ECG and echocardiography at 4, 8, and 12 months. • AF groups underwent ILR implant

Correlation of Echo with EA Mapping Markers of La

Disease

Correlation of Echo with EA Mapping Markers of La

Disease

• AF burden in Medication Group: 8% (3-53%)

• AF burden in Ablation Group: 0% (0-1%)

• The echo is a good measure of LA reserve and extent of remodeling

https://doi.org/10.1016/j.hrthm.2015.10.028

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Effect of Ablation vs. Med Management of LA Remodeling

Effect of Ablation vs. Med Management of LA Remodeling

• AF Burden ≥ 10% predicted significant drop in strain (remodeling)

• P wave duration and dispersion significantly increased in medical management group , not ablation group

• Inclusion of co-morbidities in regression models did not attenuate between group differences based on presence of AF


How long are we waiting?STAR AF II

How long are we waiting?STAR AF II

• 589 Persistent AF assigned to PVI, PVI+complex EGM, PVI+lines (roof, mitral valve isthmus) in a 1:4:4 ratio

• 48 centers in 12 countries • Failed >=1 AAD• Continued AAD use

allowed • Enrolled between 2010-

2012

Verma A et al. NEJM 2015; 372:1812-22

Longer Waiting Time After AF Dx Decreases AF Ablation Success?

Intermountain Healthcare database N=4535

Longer Waiting Time After AF Dx Decreases AF Ablation Success?

Intermountain Healthcare database N=4535

Bunch TJ et al. Heart Rhythm 2013;10:1257-1262

30-180 days


Elephant in The Room: Modifiable AF Risk FactorsElephant in The Room: Modifiable AF Risk Factors

Prathak et al, JACCEP 2017

https://doi.org/10.1016/j.jacep.2016.12.015.

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Race-3Race-3Patients with CHF and Afib randomized to rhythm control with and without (i) MRA, (ii) statins, (iii) ACE-I and/or ARB, and (iv) cardiac rehabilitation

Rienstra et al, EHJ 2018

ConclusionsConclusions• Atrial fibrillation carries risk of significant

morbidity and mortality

• Risk Factor Modification is Critical

• Successful suppression (burden less than 10%) is likely safe and effective

• Progression of AF should be countered with early ablation as:

‒ Progressive disease make the outcomes worse for PAF

‒ Persistent AF has worse outcome

‒ Early ablation confers better response

The ablation procedureThe ablation procedure

Video of Ablation Procedure

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